Among drugs, lipophilic drugs show a high cure rate by enhancing the absorption and metabolism of drugs due to high permeability across cell lipid membranes (1). Therefore, great interest has been brought to the development of the drugs (2). However, to improve the bioavailability of the lipophilic drugs, the lipophilic drugs should first be dissolved in a proper solvent, and then used. 40% of the lipophilic drugs have not appeared in the pharmaceutical market due to the lack of proper solvents and drug delivery systems (3, 4). Using an organic solvent is the method most widely used to improve the solubility of such lipophilic drugs, but there are biological safety issues and various adverse side effects caused by the use of the organic solvent (5). Owing to these problems, a non-solvent drug delivery system (DDS) capable of safely delivering various types of lipophilic drugs without using a solvent is required.
The non-solvent delivery system refers to a system that can deliver a drug without using a solubilizing solvent for lipophilic drugs in the form of crude powder. The lipophilic drugs in the form of crude powder used so far may be transdermally delivered for surgical operation (8), or may be applied to nasal drug delivery using a high-pressure powder spray mechanism (9). Such a nasal drug delivery system cannot be used for general methods for lipophilic drug delivery since a dose of the drug cannot be easily adjusted through spraying (10), and airway hypersensitivity and infections are caused by repeated absorption of drugs through the nasal cavities (11). Oral lipophilic drug delivery has a probability of overcoming the limitations of the above-described nasal drug delivery, but the bioavailability of the drugs may be lowered since the drugs undergo first pass metabolism in the liver. Based on this situation, the transdermal drug delivery system is a useful drug delivery route for lipophilic drugs in the following aspects: (i) the dose of the drug may be easily adjusted (12), (ii) adverse reactions may be reduced (13), and (iii) a first pass metabolism effect may be avoided. However, it is very difficult to deliver a powder-type lipophilic drug through the skin barrier without solubilizing the lipophilic drug. For this reason, the present inventors have developed a smart polymer system (SPS) capable of dissolving a lipophilic drug in the form of crude powder in a biodegradable polymer without using a solubilizing solvent for the lipophilic drug, and have developed a transdermal drug delivery system capable of overcoming the skin barrier and thus delivering the powder-type lipophilic drug by manufacturing a biodegradable microneedle for the smart polymer system.
Since the drug delivery system of the present invention using a biodegradable polymer requires no solvent to dissolve a lipophilic drug, the drug delivery system may be widely used to deliver various lipophilic drugs without any limitation on the solvent, and may be used as a novel lipophilic drug delivery system capable of overcoming the limitations of the oral and nasal drug delivery using as a drug delivery mechanism a transdermal drug delivery system such as biodegradable microneedles configured to form cracks through a skin barrier and disperse a drug through layers of the skin.
Throughout this specification, a number of research papers and patent documents are cited and provided in parentheses. The disclosures of the cited research papers and patent documents are incorporated herein by reference in their entirety to more fully describe the state of the art to which the present invention pertains and the content of the present invention.